Rest–activity rhythm as a clinical biomarker in cancer – Authors' reply
Authors: Hongliang Feng, Lulu Yang, Sizhi Ai, Yun Kwok Wing, Jihui Zhang
Journal: The Lancet Healthy Longevity (2023)

We thank Pasquale F Innominato and colleagues for their important comments on our Article.1Feng H Yang L Ai S et al.Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank.Lancet Healthy Longev. 2023; 4: e200-e210Summary Full Text Full Text PDF Google Scholar We agree that our study could be improved by including the actigraphic dichotomy index (I<O), an index of rest–activity rhythm.2Minors D Akerstedt T Atkinson G et al.The difference between activity when in bed and out of bed.Chronobiol Int. 1996; 13: 27-34Crossref PubMed Google Scholar A low I<O indicates weak rest–activity rhythmicity. Similarly to relative amplitude, I<O is insensitive to the absolute value and outliers of activity and does not rely on the shape of rest–activity rhythm. This index has been shown to be an excellent predictor of clinical outcomes such as survival, particularly among patients with cancer.3Lévi F Dugué P-A Innominato P et al.Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival.Chronobiol Int. 2014; 31: 891-900Crossref PubMed Google Scholar, 4Kos M Brouwer CG van Laarhoven HWM Hopman MTE van Oijen MGH Buffart LM The association between wearable device metrics and clinical outcomes in oncology: a systematic review with evidence synthesis and meta-analysis.Crit Rev Oncol Hematol. 2023; 185103979 Google Scholar We believe that I<O has great potential for the prediction of universal health outcomes. We also agree with Innominato and colleagues that the large accelerometer dataset from the UK Biobank provides a unique opportunity to investigate the predictive performance of I<O. However, we were unable to include I<O in our analyses due to scarce information on the time that participants spent in and out of bed, which is necessary for the calculation of the index. In previous studies, participants used a sleep diary or event marker button to record their time spent in and out of bed,5Natale V Innominato PF Boreggiani M et al.The difference between in bed and out of bed activity as a behavioral marker of cancer patients: a comparative actigraphic study.Chronobiol Int. 2015; 32: 925-933Crossref PubMed Scopus (20) Google Scholar but no sleep diary or log assessments were recorded as part of the UK Biobank data and event marker buttons were not included in the accelerometry devices worn by participants. As previously reported,4Kos M Brouwer CG van Laarhoven HWM Hopman MTE van Oijen MGH Buffart LM The association between wearable device metrics and clinical outcomes in oncology: a systematic review with evidence synthesis and meta-analysis.Crit Rev Oncol Hematol. 2023; 185103979 Google Scholar participants’ time in and out of bed can be obtained via visual inspection. However, conducting visual reports and inspections of each day's data for more than 90 000 raw 7-day accelerometer datasets would add an unmanageable workload to the study. Therefore, the use of well established automatic algorithms to record participants’ time in and out of bed could be a promising approach for future research. In conclusion, although we were not able to confirm Innominato and colleagues’ speculation, we agree that further research is needed to test the associations between I<O and universal health outcomes, particularly in individuals with cancer. Author declarations remain the same as in the original Article. Rest–activity rhythm as a clinical biomarker in cancerIn their Article, Hongliang Feng and colleagues1 analysed accelerometer time series data and showed a strong association between a low amplitude of rest–activity rhythm and increased disease incidence and mortality. The authors’ findings support the previously acknowledged link between circadian disruption and cancer risk.2 We commend their thorough analytical approach in such a large dataset. Full-Text PDF Open AccessAssociation between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK BiobankOur results suggest that low rest–activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest–activity rhythm to improve health and longevity. Full-Text PDF Open Access